## Role of β2-Microglobulin in MHC Class I Stability **Key Point:** β2-microglobulin is a non-covalently associated light chain that is essential for the structural integrity and cell surface expression of MHC class I molecules. ### Structure and Function MHC class I molecules consist of: 1. A heavy chain (α chain) with three extracellular domains 2. β2-microglobulin — a 12 kDa protein encoded on chromosome 15 (not chromosome 6 like MHC genes) **High-Yield:** β2-microglobulin binds to the α3 domain of the heavy chain and stabilizes the entire complex. Without β2-microglobulin, the heavy chain cannot fold properly and is rapidly degraded. ### Distinction from Other Molecules | Molecule | Function | Timing | |----------|----------|--------| | β2-microglobulin | Stabilizes mature MHC-I on surface | After peptide loading | | Tapasin | Facilitates peptide loading in ER | During assembly | | Calreticulin | Chaperone during assembly | During assembly | | TAP1/TAP2 | Transports peptides into ER | Before peptide binding | **Clinical Pearl:** In β2-microglobulin deficiency, MHC class I molecules are not expressed on the cell surface, leading to impaired CD8+ T cell recognition and increased susceptibility to intracellular pathogens. **Mnemonic:** **STAB** — β2-microglobulin **Stab**ilizes the MHC-I complex for surface presentation.
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